Category: Neurology

Reduction of serotonin transporters of patients with chronic fatigue syndrome

Abstract:

To assess the involvement of serotonin in the symptoms of chronic fatigue syndrome, we investigated the serotonergic neurotransmitter system of chronic fatigue syndrome patients by the positron emission tomography (PET).

Here we show that the density of serotonin transporters (5-HTTs) in the brain, as determined by using a radiotracer, [C](+)McN5652, was significantly reduced in the rostral subdivision of the anterior cingulate as compared with that in normal volunteers. This subdivision is different from that in the dorsal anterior cingulate in which binding potential values of individual patient showed a weak negative correlation with self-reported pain score of the patients.

Therefore, an alteration of serotonergic system in the rostral anterior cingulate plays a key role in pathophysiology of chronic fatigue syndrome.

 

Source: Yamamoto S, Ouchi Y, Onoe H, Yoshikawa E, Tsukada H, Takahashi H, Iwase M, Yamaguti K, Kuratsune H, Watanabe Y. Reduction of serotonin transporters of patients with chronic fatigue syndrome. Neuroreport. 2004 Dec 3;15(17):2571-4. http://www.ncbi.nlm.nih.gov/pubmed/15570154

 

Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome

Abstract:

BACKGROUND: Fatigue is a crucial sensation that triggers rest, yet its underlying neuronal mechanisms remain unclear. Intense long-term fatigue is a symptom of chronic fatigue syndrome, which is used as a model to study the mechanisms underlying fatigue.

METHODS: Using magnetic resonance imaging, we conducted voxel-based morphometry of 16 patients and 49 age-matched healthy control subjects.

RESULTS: We found that patients with chronic fatigue syndrome had reduced gray-matter volume in the bilateral prefrontal cortex. Within these areas, the volume reduction in the right prefrontal cortex paralleled the severity of the fatigue of the subjects.

CONCLUSION: These results are consistent with previous reports of an abnormal distribution of acetyl-L-carnitine uptake, which is one of the biochemical markers of chronic fatigue syndrome, in the prefrontal cortex. Thus, the prefrontal cortex might be an important element of the neural system that regulates sensations of fatigue.

 

Source: Okada T, Tanaka M, Kuratsune H, Watanabe Y, Sadato N. Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome. BMC Neurol. 2004 Oct 4;4(1):14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC524491/

 

Altered central nervous system signal during motor performance in chronic fatigue syndrome

Abstract:

OBJECTIVE: The purpose of this study was to determine whether brain activity of chronic fatigue syndrome (CFS) patients during voluntary motor actions differs from that of healthy individuals.

METHODS: Eight CFS patients and 8 age- and gender-matched healthy volunteers performed isometric handgrip contractions at 50% maximal voluntary contraction level. They first performed 50 contractions with a 10 s rest between adjacent trials–‘Non-Fatigue’ (NFT) task. Subsequently, the same number of contractions was performed with only a 5 s rest between trials–‘Fatigue’ (FT) task. Fifty-eight channels of surface EEG were recorded simultaneously from the scalp. Spectrum analysis was performed to estimate power of EEG frequency in different tasks. Motor activity-related cortical potential (MRCP) was derived by triggered averaging of EEG signals associated with the muscle contractions.

RESULTS: Major findings include: (i) Motor performance of the CFS patients was poorer than the controls. (ii) Relative power of EEG theta frequency band (4-8 Hz) during performing the NFT and FT tasks was significantly greater in the CFS than control group (P < 0.05). (iii) The amplitude of MRCP negative potential (NP) for the combined NFT and FT tasks was higher in the CFS than control group (P < 0.05) (iv) Within the CFS group, the NP was greater for the FT than NFT task (P<0.01), whereas no such difference between the two tasks was found in the control group.

CONCLUSIONS: These results clearly show that CFS involves altered central nervous system signals in controlling voluntary muscle activities, especially when the activities induce fatigue.

SIGNIFICANCE: Physical activity-induced EEG signal changes may serve as physiological markers for more objective diagnosis of CFS.

 

Source: Siemionow V, Fang Y, Calabrese L, Sahgal V, Yue GH. Altered central nervous system signal during motor performance in chronic fatigue syndrome. Clin Neurophysiol. 2004 Oct;115(10):2372-81. http://www.ncbi.nlm.nih.gov/pubmed/15351380

 

Detection of antibody against Borna disease virus-p24 in the plasma of Chinese patients with chronic fatigue syndrome by Western-blot analysis

Abstract:

OBJECTIVE: To evaluate the prevalence of infection with Borna disease virus (BDV) in Chinese patients with chronic fatigue syndrome (CFS) and control subjects, and to discuss the etiological association between CFS and infection with BDV.

METHODS: The CDC (1994) diagnostic criteria for CFS were used for case definition. Sixty-one patients suffered from CFS were from 11 Provinces in China. To detect the antibody against BDV-p24 on the plasma samples from all cases and 73 healthy control subjects by Western-blotting analysis.

RESULTS: 7 of the sixty-one cases and 0 of the controls were sero-positive for BDV-p24 antibody, there was a statistical significant difference between the two groups (11.48% vs 0%; P less than 0.010).

CONCLUSION: Chinese patients with CFS showed sero-positive identifying BDV infection, by comparison, anti.BDV-p24 antibody prevalence in patients was significantly higher than in controls. An etiological association may exist between CFS and BDV infection.

 

Source: Li YJ, Wang DX, Zhang FM, Liu ZD, Yang AY, Ykuta K. Detection of antibody against Borna disease virus-p24 in the plasma of Chinese patients with chronic fatigue syndrome by Western-blot analysis. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2003 Dec;17(4):330-3. [Article in Chinese] http://www.ncbi.nlm.nih.gov/pubmed/15340544

 

Use of time-frequency analysis to investigate temporal patterns of cardiac autonomic response during head-up tilt in chronic fatigue syndrome

Abstract:

Although a number of studies have reported alterations in cardiac autonomic nervous system function in chronic fatigue syndrome (CFS), the results are not consistent across studies. Reasons for these discrepancies include (1) the use of a heterogeneous patient sample that included those with orthostatic postural tachycardia (POTS), a condition with an autonomic changes, and (2) the use of frequency domain techniques which require a stationary signal and averaging data across relatively long epochs.

To deal with these shortcomings, we used the smoothed pseudo-Wigner-Ville transform (SPWVT) to analyze heart rate variability (HRV) and blood pressure variability (BPV) during head-up tilt (HUT) by separating CFS patients into those with and without POTS. SPWVT has the advantage of providing instantaneous information about autonomic function under nonstable physiological conditions. We studied 18 CFS patients without POTS, eight CFS patients with POTS and 25 sedentary healthy controls during supine rest and during the first 10 min after HUT.

While we found significant effects of postural change in both groups for all autonomic variables, there were significant group x time interactions between CFS without POTS and controls for only instant center frequency (ICF) within the low frequency region both from HRV (p=0.02) and from BPV (p=0.01). Although the physiological meaning of ICF still remains unknown, the data suggest that even CFS patients without POTS may have a subtle underlying disturbance in autonomic function.

 

Source: Yoshiuchi K, Quigley KS, Ohashi K, Yamamoto Y, Natelson BH. Use of time-frequency analysis to investigate temporal patterns of cardiac autonomic response during head-up tilt in chronic fatigue syndrome. Auton Neurosci. 2004 Jun 30;113(1-2):55-62. http://www.ncbi.nlm.nih.gov/pubmed/15296795

 

Neural correlates of the chronic fatigue syndrome–an fMRI study

Abstract:

Chronic fatigue syndrome (CFS) is characterized by a debilitating fatigue of unknown aetiology. Patients who suffer from CFS report a variety of physical complaints as well as neuropsychological complaints. Therefore, it is conceivable that the CNS plays a role in the pathophysiology of CFS. The purpose of this study was to investigate neural correlates of CFS, and specifically whether there exists a linkage between disturbances in the motor system and CFS.

We measured behavioural performance and cerebral activity using rapid event-related functional MRI in 16 CFS patients and 16 matched healthy controls while they were engaged in a motor imagery task and a control visual imagery task. CFS patients were considerably slower on performance of both tasks, but the increase in reaction time with increasing task load was similar between the groups.

Both groups used largely overlapping neural resources. However, during the motor imagery task, CFS patients evoked stronger responses in visually related structures. Furthermore, there was a marked between-groups difference during erroneous performance. In both groups, dorsal anterior cingulate cortex was specifically activated during error trials. Conversely, ventral anterior cingulate cortex was active when healthy controls made an error, but remained inactive when CFS patients made an error.

Our results support the notion that CFS may be associated with dysfunctional motor planning. Furthermore, the between-groups differences observed during erroneous performance point to motivational disturbances as a crucial component of CFS.

 

Source: de Lange FP, Kalkman JS, Bleijenberg G, Hagoort P, van der Werf SP, van der Meer JW, Toni I. Neural correlates of the chronic fatigue syndrome–an fMRI study. Brain. 2004 Sep;127(Pt 9):1948-57. Epub 2004 Jul 7. http://brain.oxfordjournals.org/content/127/9/1948.long (Full article)

 

Acetylcholine mediated vasodilatation in the microcirculation of patients with chronic fatigue syndrome

Abstract:

The aetiology of chronic fatigue syndrome (CFS) remains controversial and a number of hypotheses have been put forward to explain it. Research into the condition is hindered by the considerable heterogeneity seen across patients but several reports have highlighted disturbances to cholinergic mechanisms in terms of central nervous system activity, neuromuscular function and autoantibodies to muscarinic cholinergic receptors. This paper examines an altogether separate function for acetylcholine and that is its role as an important and generalized vasodilator.

Most diseases are accompanied by a blunted response to acetylcholine but the opposite is true for CFS. Such sensitivity is normally associated with physical training so the finding in CFS is anomalous and may well be relevant to vascular symptoms that characterise many patients. There are several mechanisms that might lead to ACh endothelial sensitivity in CFS patients and various experiments have been designed to unravel the enigma. These are reported here.

 

Source: Spence VA, Khan F, Kennedy G, Abbot NC, Belch JJ. Acetylcholine mediated vasodilatation in the microcirculation of patients with chronic fatigue syndrome. Prostaglandins Leukot Essent Fatty Acids. 2004 Apr;70(4):403-7. http://www.ncbi.nlm.nih.gov/pubmed/15041034

 

Autonomic function and serum erythropoietin levels in chronic fatigue syndrome

Abstract:

OBJECTIVE: Given previous findings, we wished to investigate whether there was evidence of autonomic dysfunction in patients with chronic fatigue syndrome, and whether this could be related to reduced erythropoietin levels and altered red blood cell indices.

METHODS: We assessed autonomic function and analysed blood parameters (including erythropoietin) in 22 patients with chronic fatigue syndrome who were medication-free and without comorbid depression or anxiety. Results were compared to 23 iron-deficiency anaemia patients and 18 healthy individuals.

RESULTS: Autonomic testing in patients with chronic fatigue syndrome yielded a significantly greater increase in heart rate together with a more pronounced systolic blood pressure fall on standing compared to healthy individuals. Heart rate beat-to-beat variation on deep breathing and responses to the Valsalva manoeuvre were normal. Two of 22 patients with chronic fatigue had mild normochromic normocytic anaemia with normal ferritin, vitamin B12 and folate levels. Serum erythropoietin levels were within reference range.

CONCLUSION: Some autonomic dysfunction is present in chronic fatigue syndrome (CFS) patients; the explanation remains uncertain, but could relate to cardiovascular deconditioning. There were no major haematological, biochemical or immunological abnormalities in these patients.

 

Source: Winkler AS, Blair D, Marsden JT, Peters TJ, Wessely S, Cleare AJ. Autonomic function and serum erythropoietin levels in chronic fatigue syndrome. J Psychosom Res. 2004 Feb;56(2):179-83. http://www.ncbi.nlm.nih.gov/pubmed/15016575

 

Plasma endothelin-1 levels in chronic fatigue syndrome

Comment on: Increased plasma endothelin-1 levels in fibromyalgia syndrome. [Rheumatology (Oxford). 2003]

 

SIR, We read with interest the report by Pache et al. [1] showing increased endothelin-1 (ET-1) levels in patients with a diagnosis of fibromyalgia syndrome (FMS) and their conclusion that elevated ET-1 levels might contribute to some of the apparent vascular disturbances that characterize the syndrome. Pache et al. also point to the overlap between the clinical presentation of FMS and other ‘stress-associated disorders including chronic fatigue syndrome (CFS) and depression’. Whether FMS or CFS is stress-induced is a contentious issue in itself, but of equal concern is the view that FMS should be considered to be part of the spectrum of illness under the generic name ‘chronic fatigue syndrome’. Clearly, the symptoms of FMS and CFS have much in common [2, 3] but it has been said that FMS represents an additional burden of suffering among those with CFS [4], those patients meeting the case definitions for both FMS and CFS having a worse course, worse overall health and greater disease impact [2]. Furthermore, while many FMS patients experience fatigue, it has been estimated that only about one-fifth fulfil the specific criteria required for CFS [5]. Clinical similarities apart, there are biological differences between the two; for example, cerebrospinal fluid levels of substance P are elevated in FMS but not in CFS patients [6], and cardiovascular responses to postural challenge are characteristic of many CFS patients but are not apparent in those with FMS [7].

You can read the rest of this comment here: http://rheumatology.oxfordjournals.org/content/43/2/252.long

 

Source: Kennedy G, Spence V, Khan F, Belch JJ. Plasma endothelin-1 levels in chronic fatigue syndrome. Rheumatology (Oxford). 2004 Feb;43(2):252-3; author reply 253-4. http://rheumatology.oxfordjournals.org/content/43/2/252.long (Full article)

 

Association between serotonin transporter gene polymorphism and chronic fatigue syndrome

Abstract:

Interaction between the hypothalamo-pituitary-adrenal axis and the serotonergic system is thought to be disrupted in chronic fatigue syndrome(CFS) patients. We examined a serotonin transporter (5-HTT) gene promoter polymorphism, which affects the transcriptional efficiency of 5-HTT, in 78 CFS patients using PCR amplification of the blood genomic DNA.

A significant increase of longer (L and XL) alleic variants was found in the CFS patients compared to the controls both by the genotype-wise and the allele-wise analyses (both p<0.05, by chi(2) test and Fisher’s exact test). Attenuated concentration of extracellular serotonin due to longer variants may cause higher susceptibility to CFS.

 

Source: Narita M, Nishigami N, Narita N, Yamaguti K, Okado N, Watanabe Y, Kuratsune H. Association between serotonin transporter gene polymorphism and chronic fatigue syndrome. Biochekm Biophys Res Commun. 2003 Nov 14;311(2):264-6. http://www.ncbi.nlm.nih.gov/pubmed/14592408